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RUPPERT, DAVID STRATER. a Study of Osseointegration of Additively Manufactured Implants in Rats Through Vibration and Ultrasound

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RUPPERT, DAVID STRATER. a Study of Osseointegration of Additively Manufactured Implants in Rats Through Vibration and Ultrasound Abstract: RUPPERT, DAVID STRATER. A Study of Osseointegration of Additively Manufactured Implants in Rats through Vibration and Ultrasound. (Under the direction of Paul S. Weinhold, PhD and Ola L.A. Harrysson, PhD) Amputees frequently develop soft tissue problems on their residual limb due to increased pressure and shear-forces generated at the socket-limb interface. Direct skeletal attachment of prostheses via percutaneous osseointegrated implants provides stable connections while eliminating skin lesions. However, effective osseointegration of implants remains a major clinical challenge. Hastening rehabilitation, as-well-as providing implants for patient specific anatomy, would greatly increase the feasibility of percutaneous osseointegrated prostheses as an alternative to socket prosthetics. Previous studies indicate that vibration and low-intensity pulsed ultrasound (LIPUS) are beneficial for bone healing. However, the optimal vibration amplitude hasn’t been identified nor has it been shown that LIPUS has a beneficial effect in an intramedullary model to stimulate healing at the bone-implant interface. The primary objective of this work was identifying therapies for accelerating implant osseointegration. Whole body vibration at various amplitudes was investigated to identify the optimal stimuli. Locally applied vibration and LIPUS were studied separately and cumulatively. Non-patient specific threaded implants are being used in FDA clinical osseointegrated prostheses trials. Additive manufacturing can cost effectively create custom implants to better interface with amputees’ residual bones. A secondary objective of this study was evaluating additive manufacturing as an alternative to commonly used Brånemark threaded implant to produce patient specific implants. This objective was broken into two phases: compare osseointegration of additive manufactured (AM) implants to threaded implants; compare osseointegration strength of coarse and fine textured AM implants. The two objectives were carried out through three studies. The first study was split into two cohorts of Sprague-Dawley rats receiving bilateral, titanium implants (AM vs. threaded) in their tibiae. One cohort, comprising five groups vibrated at 45Hz: 0.0 (control), 0.15, 0.3, 0.6 or 1.2g, was followed for 6weeks. A second cohort, divided into two groups (control and 0.6g), was followed for 24 days. Osseointegration was evaluated through mechanical, µCT and histological evaluations. Bone-volume fraction around the implant increased at 0.6g compared to control. The AM implants exhibited significantly improved mechanical stability relative to their threaded counterparts. The second study comprised of two cohorts receiving bilateral, titanium implants in their distal femurs and were followed for 4weeks. The first cohort received coarse AM implants produced by electron-beam melting (EBM) transcortically in one femur and a direct melt laser- sintered (DMLS) fine textured AM implant in the contralateral femur. The second cohort received DMLS implants (either fine textured or coarse textured to mimic EBM) in the intramedullary canal of each femur. Osseointegration was evaluated through mechanical and µCT evaluation. The fixation strength of coarse textured implants provided superior interlocking relative to fine textured implants without affecting bone morphology in both cohorts. The bilateral femoral intramedullary implant model of the third study looked at effects of local vibration and LIPUS on early osseointegration (4weeks) and the separate and combined effects of these treatments on midterm osseointegration (8weeks). Osseointegration was evaluated through mechanical, µCT and histological evaluations. LIPUS produced increased pushout load relative to control at 4weeks. Both µCT and histology revealed treatment with either LIPUS or vibration increased bone around the implant relative to controls at 4weeks. No differences were noted in pushout loads at 8weeks. The bone gained with LIPUS at 4weeks was no longer present at 8weeks. Vibration treatment resulted in greater bone around the implant than all other groups at 8weeks. These studies demonstrate the potential benefit of LIPUS as a therapeutic tool for reducing amputees’ rehabilitation period and the use of vibration for preventing bone resorption during the rehabilitation period while the limb isn’t yet loaded. Additive manufacturing was also shown as a viable alternative to current production methods, opening the way to fabrication of patient specific implants. A Study of Osseointegration of Additively Manufactured Implants in Rats through Vibration and Ultrasound By David Strater Ruppert A dissertation submitted to the Graduate Faculty of North Carolina State University in partial fulfillment of the requirements for the degree of Doctor of Philosophy Biomedical Engineering Raleigh, North Carolina 2017 APPROVED BY: _______________________________ _______________________________ Denis J. Marcellin-Little, DEDV He Huang, PhD _______________________________ Richard Wysk, PhD _______________________________ _______________________________ Ola L.A. Harrysson, PhD Paul S. Weinhold, PhD Committee Chair Committee Co-Chair Biography: David Ruppert is a PhD candidate in the NCSU/UNC joint BME program. He has a Masters in mechanical engineering from Virginia Tech where he focused in biomechanics and equine rehabilitation. Ruppert also has over 10 years of experience developing novel technologies for industry. His current research is in improving mechanical stability and accelerating osseointegration of titanium implants. After earning his Bachelor of Science in Mechanical Engineering from the University of Maine in Orono in 1997 he started his career at Steag Hamatech. As a mechanical engineer he supported designers through analytical calculations, FEA, and experimentation. In 1998 he joined the research and development department where he designed and completed research projects for various processes, designed solutions to improve yields and reliability of machines and managed the summer engineering interns. While at Steag Hamatech he developed a thermal management system to robustly manufacture the emerging DVD technology. He designed a robot handling system to create the most compact CD manufacturing machine on the market. He also worked with a team to produce a repeatable coating process for bonding the DVD substrates. In 2000 he was invited as a fully funded graduate student to attend Virginia Tech’s Mechanical Engineering Master’s program to focus in biomechanics. He performed equine gait analyses and designed a robotic simulator to test a rehabilitation device he had also conceptualized to earn his degree. While at Virginia Tech, he also conducted undergraduate labs and graded reports for Junior and Senior level students. He was responsible for maintaining the undergraduate laboratory equipment and trained fellow teacher’s assistants. ii In 2003 Ruppert joined D2 Inline Solutions, a small startup company, as the senior mechanical engineer providing design-leadership to designers for product development. During his two years there he created revolutionary equipment for the vacuum metallization process. As the senior engineer, he developed the primary intellectual property for the company including a novel valve sealing surface and a helium cooling process for vacuum metallization equipment that went on to be patented and acquired by an international company. In 2005 he started his own engineering consulting service where he provided to industry: thermal, fluid, and structural analysis, kinematic and dynamic analysis, specification of mechanical components based on load calculations. He recommended initial designs and design modifications to draftspersons in order to document and modify designs. He also checked detail and assembly drawings for correct design intent. Later in 2005, Ruppert went to Clyde Bergemann Bachmann as their Finite Element Analyst where he provided finite element analysis for all of the engineering teams designing stack, diverter, louvers and dampers for various industries. The analysis included structural analysis per customer specified standards and codes; thermal and fluid flow models; hand calculations as well as checking other engineers’ hand calculations; and providing the knowledge base for technical analysis of structures to engineering teams. He moved from industry to academia in 2012 to pursue a PhD in Biomedical Engineering through the joint program of the University of North Carolina and the North Carolina State University. He investigated the effects of various amplitudes of whole body vibration, locally applied vibration and low intensity pulsed ultrasound on bone ongrowth in an osseointegration rodent model. His research also spread into the evaluation of various additive manufacturing iii processes for improving mechanical stability of osseointegrated implants. His research was funded by the Dean’s Fellowship, a NC Tracs grant, an NSF grant and a teaching assistantship. He functioned as the lead lecturer for the course Biomedical Engineering Design and Manufacturing II in the spring of 2017. In that role he redesigned the course syllabus from a reverse engineering project to needs-based innovation project. He also organized guest lecturers on various topics from Modern Manufacturing Techniques to Market Analysis and FDA Regulatory Pathways. Ruppert intends to transition back into industry to develop and design assistive technology for the rehabilitation engineering flied. iv
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